MariTide (AMG 133)

Human clinical Weight Loss & Metabolism 2 sources

MariTide (AMG 133) is an investigational bispecific molecule developed by Amgen that uniquely combines a glucagon-like peptide-1 (GLP-1) receptor agonist with a gastric inhibitory polypeptide (GIP) receptor antagonist. Unlike other dual-action drugs that activate both receptors, it activates GLP-1 while blocking GIP, which research suggests may lead to significant, sustained weight loss with less frequent dosing.

01Dosing reference

Amount

Investigational (e.g., 140 mg to 420 mg in trials)

Frequency

Once monthly (every 4 weeks)

Cycle

Continuous monthly dosing in clinical trials

Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

GLP-1 Receptor Agonism

Activates the GLP-1 receptor to slow gastric emptying, increase satiety, and regulate blood sugar levels.

GIP Receptor Antagonism

Blocks the GIP receptor, which in preclinical models has been shown to enhance weight loss and improve metabolic parameters when combined with GLP-1 activation.

Extended Half-Life via Antibody Conjugation

The peptide is conjugated to a monoclonal antibody backbone, significantly extending its half-life and allowing for monthly or even less frequent dosing.

03Human evidence

Phase 1 trials showed significant, dose-dependent weight loss (up to 14.5% after 85 days) with an acceptable safety profile.

Phase 1 randomized, double-blind, placebo-controlled study in obese participants without diabetes.

Phase 2 trials indicated substantial and sustained weight reduction over 52 weeks, supporting its potential as a monthly or less frequent injection.

Phase 2 clinical trial evaluating multiple dosing regimens in overweight or obese adults.

04Preclinical evidence

Combining GIP antagonism with GLP-1 agonism resulted in greater weight loss than GLP-1 agonism alone.

Studies in diet-induced obese mice comparing dual action versus single receptor activation.

Sustained reductions in body weight and food intake were observed with infrequent dosing.

Pharmacokinetic and pharmacodynamic studies in cynomolgus monkeys.

05What is known vs. unknown

Reasonably established

MariTide is a first-in-class bispecific molecule acting as a GIPR antagonist and GLP-1R agonist.
It is designed for less frequent dosing, potentially once monthly or less, due to its extended half-life.
Clinical trials have demonstrated significant and rapid weight loss in obese individuals.
It is currently under investigation by Amgen and is not yet FDA-approved.

Unknowns & limits

Long-term safety and cardiovascular outcomes are not yet fully established.
The exact long-term implications of chronic GIP receptor antagonism in humans remain under investigation.
Optimal dosing regimens for maintenance of weight loss after the initial reduction phase are still being determined.

06Safety & regulatory context

Regulatory statusMariTide is an investigational drug and is not FDA-approved for any indication. In clinical trials, the most common adverse events have been gastrointestinal in nature, such as nausea and vomiting, which are typical for GLP-1 receptor agonists. Its long-term safety profile, particularly concerning the novel mechanism of GIP antagonism, is still being evaluated in ongoing Phase 2 and Phase 3 trials.

07Compared with Tirzepatide

MariTide (AMG 133) vs. Tirzepatide

Key difference

Tirzepatide is a dual GIP and GLP-1 receptor agonist, whereas MariTide is a GLP-1 receptor agonist but a GIP receptor antagonist.

When researchers discuss each

Researchers discuss Tirzepatide when exploring the synergistic effects of activating both receptors, while MariTide is discussed when investigating the potential benefits of blocking GIP while activating GLP-1 for potentially longer-lasting weight loss.

08Glossary

Agonist

A substance that binds to a receptor and activates it to produce a biological response.

Antagonist

A substance that binds to a receptor but does not activate it, blocking the receptor's natural function.

Bispecific Molecule

A molecule engineered to bind to two different targets simultaneously.

09Knowledge check

Q1What is the unique dual mechanism of action of MariTide (AMG 133)?

Q2What is a significant potential advantage of MariTide's pharmacokinetic profile?

Q3Which statement best describes a documented limitation of the clinical evidence for MariTide (AMG 133) in the dossier?

Q4When researchers contrast MariTide with tirzepatide, what research question is consistent with the dossier's stated comparison context?

Q5Which statement accurately reflects MariTide’s regulatory and safety status as described in the dossier?

10Sources

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Research and educational use onlyNothing on this site is medical advice, a prescription, or a recommendation for human use. Compounds documented here are research chemicals. Consult a qualified clinician before making any health decision.